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Mechanisms of long-term survival of self-reactive helper T cells

Research Project

Project/Area Number 19K07488
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionKeio University

Principal Investigator

CHIKUMA Shunsuke  慶應義塾大学, 医学部(信濃町), 准教授 (50437208)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自己免疫疾患 / ヘルパーT細胞 / Th17 / 慢性炎症 / ヘルパーT細胞 / メモリーT細胞 / T細胞 / 免疫記憶
Outline of Research at the Start

乾癬、リウマチ性関節炎、全身性エリテマトーデス、多発性硬化症といった自己免疫疾患は近年増加の一途をたどり、この病態解明は社会的に緊急かつ重要な課題である。自己免疫疾患の多くは、IL-17産生性ヘルパーT細胞(Th17)によって起こり、寛解と再燃を繰り返す特徴がある。本研究ではTh17依存性自己免疫疾患モデルを用いて、自己反応性Th17が体内において長期間生存し、再活性化して炎症の再燃を起こすメカニズムを探求する。

Outline of Final Research Achievements

IL-17 producing helper T cells (Th17) are suggested in persistent autoimmune diseases. We found that autoreactive Th17 are preferentially maintained and activated in lymphopenic mice and caused severe autoimmune diseases. In addition, mice treated with a cocktail of antibiotics that depleted intestinal microbiota showed almost complete protection from Th17-mediated autoimmunity. Our current data suggest that autoreactive T cells are maintained by intestinal microbiota. Modulating particular intestinal bacteria may provide novel therapy for many autoimmune diseases.

Academic Significance and Societal Importance of the Research Achievements

乾癬、リウマチ性関節炎、全身性エリテマトーデス、多発性硬化症といった慢性の自己免疫疾患は近年増加の一途をたどり、この病態解明は社会的に緊急かつ重要な課題である。マウスを用いて自己反応性Th17が長期生存し、慢性皮膚炎を起こすモデルを確立できた。今後は、このモデルを用いて自己免疫疾患の新規治療法を研究する予定である。また、Th17の生存や活性化に関わる菌およびその抗原などを同定できれば、自己免疫疾患のさらなる理解や治療法につながると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020 2019 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] TRIM28 Expression on Dendritic Cells Prevents Excessive T Cell Priming by Silencing Endogenous Retrovirus2021

    • Author(s)
      Chikuma Shunsuke、Yamanaka Soichiro、Nakagawa So、Ueda Mahoko Takahashi、Hayabuchi Hodaka、Tokifuji Yukiko、Kanayama Masashi、Okamura Tadashi、Arase Hisashi、Yoshimura Akihiko
    • Journal Title

      The Journal of Immunology

      Volume: 206 Issue: 7 Pages: 1528-1539

    • DOI

      10.4049/jimmunol.2001003

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of singularity in immunity and cancer by novel imaging techniques2020

    • Author(s)
      Nagai T, Chikuma S, Hanaoka K
    • Journal Title

      Biophysics and Physicobiology

      Volume: 17 Issue: 0 Pages: 98-99

    • DOI

      10.2142/biophysico.BSJ-2020018

    • NAID

      130007919806

    • ISSN
      2189-4779
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tocilizumab monotherapy uncovered the role of the CCL22/17-CCR4+ Treg axis during remission of crescentic glomerulonephritis2020

    • Author(s)
      Sakai R, Ito M, Yoshimoto K, Chikuma S, Kurasawa T, Kondo T, Suzuki K, Takeuchi T, Amano K, Yoshimura A
    • Journal Title

      Clin Transl Immunology

      Volume: 9 Issue: 11

    • DOI

      10.1002/cti2.1203

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.2020

    • Author(s)
      Kondo T, Ando M, Nagai N, Tomisato W, Srirat T, Liu B, Mise-Omata S, Ikeda M, Chikuma S, Nishimasu H, Nureki O, Ohmura M, Hayakawa N, Hishiki T, Uchibori R, Ozawa K, Yoshimura A
    • Journal Title

      Cancer Res

      Volume: 80 Issue: 3 Pages: 471-483

    • DOI

      10.1158/0008-5472.can-19-1196

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vitro Conversion of Activated T Cells into Stem Cell Memory-Like T Cells.2019

    • Author(s)
      Kondo T, Imura Y, Ando M, Chikuma S, Yoshimura A
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 41-51

    • DOI

      10.1007/978-1-4939-9728-2_4

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization, and IL-17 expression.2019

    • Author(s)
      Nakatsukasa H, Oda M, Yin J, Chikuma S, Ito M, Koga-Iizuka M, Someya K, Kitagawa Y, Ohkura N, Sakaguchi S, Koya I, Sanosaka T, Kohyama J, Tsukada YI, Yamanaka S, Takamura-Enya T, Lu Q, Yoshimura A
    • Journal Title

      International immunology

      Volume: 31 Issue: 5 Pages: 335-347

    • DOI

      10.1093/intimm/dxz008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] エピゲノム因子による、自己免疫寛容、がん免疫寛容の調節2022

    • Author(s)
      竹馬 俊介
    • Organizer
      文科省先端モデル動物支援プラットフォーム 成果発表会
    • Related Report
      2021 Annual Research Report
  • [Presentation] T細胞寛容におけるクロマチン制御因子TRIM28の機能解析2021

    • Author(s)
      竹馬 俊介
    • Organizer
      第29回京都T細胞会議
    • Related Report
      2021 Annual Research Report
  • [Book] TRIM28は内在性レトロウイルスの抑制を通じ、T細胞免疫の暴走を抑制する2022

    • Author(s)
      竹馬 俊介
    • Total Pages
      2
    • Publisher
      医学のあゆみ
    • Related Report
      2021 Annual Research Report
  • [Remarks] 慶應発サイエンス 免疫の暴走を開始時に防ぐ仕組みを解明

    • URL

      https://kompas.hosp.keio.ac.jp/contents/medical_info/science/202106.html

    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2025-03-27  

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